This project has concentrated on examining the neuronal bases for drug action by using electrophysiological recordings from a variety of in vitro preparations which provide useful models of the mammalian nervous system for studying the membrane mechanisms underlying the actions of clinically important drugs. The drugs investigated include 1) non-narcotic analgesics, 2) mitochondrial uncoupling agents, 3) convulsants and 4) general anesthetics. The primary observations are 1) non-narcotic analgesics depress neuronal excitability by non-specifically partitioning into the cell membrane; 2) mitochondrial uncoupling agents reversibly enhance cation permeability of membranes by non-specifically partitioning into membranes; 3) convulsants increase excitability by antagonizing specific effects of inhibitory neurotransmitters; 4) general anesthetics depress excitability by decreasing excitatory neurotransmitter effects and increasing inhibitory neurotransmitter actions. The results indicate that different classes of neuropharmacologically important agents act upon different neuronal membrane mechanisms and that model invertebrate and vertebrate systems are useful in elucidating mechanisms of drug action at the single cell level.